Autonomic Modulation by Electrical Stimulation of the Parasympathetic Nervous System: An Emerging Intervention for Cardiovascular Diseases

Abstract

SUMMARYThe cardiac autonomic nervous system has been known to play an important role in the development and progression of cardiovascular diseases. Autonomic modulation by electrical stimulation of the parasympathetic nervous system, which increases the parasympathetic activity and suppresses the sympathetic activity, is emerging as a therapeutic strategy for the treatment of cardiovascular diseases. Here, we review the recent literature on autonomic modulation by electrical stimulation of the parasympathetic nervous system, including vagus nerve stimulation, transcutaneous auricular vagal stimulation, spinal cord stimulation, and ganglionated plexi stimulation, in the treatment of heart failure, atrial fibrillation, and ventricular arrhythmias.The cardiac autonomic nervous system, consisting of the sympathetic and the parasympathetic components, has been shown to play an important role in many cardiovascular diseases, such as heart failure, hypertension, atrial fibrillation, and ventricular arrhythmias [1][2][3][4]. An increased sympathetic nerve activity and a reduction of vagal cardiac tone are shown to be pathogenic in most of these conditions. In light of the autonomic imbalance involved in the development and progression of cardiovascular diseases, therapeutic interventions are focused on the inhibition of the sympathetic activation such as the use of b-receptor blockers, cardiac sympathetic denervation, and renal sympathetic denervation, and the increase of the parasympathetic activity such as vagus nerve stimulation. During the last decades, dysregulation of the autonomic nervous system in cardiovascular diseases has received considerable attention and interventions aiming at autonomic rebalance are emerging as new therapeutic options for the management of cardiovascular diseases. Autonomic modulation by electrical stimulation of the autonomic nervous system has been used clinically in patients with intractable angina pectoris [5][6][7], epilepsy [8], and depression [9,10]. Here, we review the experimental studies and clinical trials that are focused on autonomic modulation by electrical stimulation of the parasympathetic nervous system (ES-PNS), including vagus nerve stimulation (VNS), transcutaneous auricular vagal stimulation (tragus stimulation, TS), spinal cord stimulation (SCS), and ganglionated plexi stimulation (GPS), in the treatment of heart failure (HF), atrial fibrillation (AF), and ventricular arrhythmias (VAs). ES-PNS and HFSympathetic activation and parasympathetic withdrawal are the characteristics of autonomic imbalance in HF [2,11,12] [19], the ANTHEM-HF Trial, in which either left or right VNS was performed using an open-loop stimulation system. However, another randomized controlled trial, the NECTAR-HF trial [20], in which 96 symptomatic HF patients were randomized in a 2:1 ratio to receive VNS or control for a 6-month period, showed that VNS failed to significantly improve the primary and secondary endpoint measures of cardiac remodeling and functional capacity, even though quality-...

Effect of electrical stimulation on blood flow velocity and vessel size

“…Nevertheless, measurement and prediction of circulatory features lack the required precision for clinical diagnosis and treatment. Previous studies have evaluated the characteristics of the vasculature and blood flow [2, 3]. Specifically, it is important to ascertain the heart rate, blood pressure, state of the blood vessels, and blood flow velocity to predict blood flow characteristics.…”

Correlation of Ventricular Arrhythmogenesis with Neuronal Remodeling of Cardiac Postganglionic Parasympathetic Neurons in the Late Stage of Heart Failure after Myocardial Infarction

“…In the present study, we found that N-type Ca 2+ currents in AVG neurons negatively correlated with the occurrence of ventricular arrhythmias in late stage CHF (Figure 7). Although it is unclear how electrical remodeling of AVG neurons links to ventricular arrhythmogenesis in late stage CHF, many studies (Brack et al, 2013; Aiba et al, 2015; He et al, 2016) provide strong evidence in support of the pivotal anti-arrhythmic effect of parasympathetic activation. Vagal nerve stimulation inhibits ventricular arrhythmias through direct or indirect activation of muscarinic acetylcholine receptors (Brack et al, 2013; He et al, 2016).…”

“…Although it is unclear how electrical remodeling of AVG neurons links to ventricular arrhythmogenesis in late stage CHF, many studies (Brack et al, 2013; Aiba et al, 2015; He et al, 2016) provide strong evidence in support of the pivotal anti-arrhythmic effect of parasympathetic activation. Vagal nerve stimulation inhibits ventricular arrhythmias through direct or indirect activation of muscarinic acetylcholine receptors (Brack et al, 2013; He et al, 2016). The parasympathetic activation induced by vagal nerve stimulation or treatment with exogenous acetylcholine suppresses the occurrence of ventricular arrhythmias and mitigates SCD in CHF (Sabbah, 2011; Aiba et al, 2015).…”

Influence of Clonidine on Antihypertensive Selective Afferent Vagal Nerve Stimulation in Rats

“…In the last years, bipolar unselective vagal neuromodulation has been investigated for several indications like sepsis, autoimmune‐diseases, obesity, headaches, obsessive‐compulsive‐disorders, and depression . By influencing the—supposed to be dysfunctional—parasympathetic cardiac activity, neuromodulation techniques like VNS seem to have positive effects especially on heart failure and—preclinically investigated—on atrial fibrillation . Significant changes in BP during unselective VNS have not been reported.…”